Microtubules exist in all eukaryotic cells and tissues. They are especially abundant in the central nervous system. Microtubules appear to be important in the maintenance of asymmetry in cell structure, and are integrally associated with several types of cellular movement. The specific roles of microtubules (neurotubules) within the central nervous system are mostly unknown. A number of chemical agents known to disrupt the organization of microtubule structures outside of the CNS exhibit striking biological effects within the central nervous system. It is likely that these effects are mediated by a molecular action on neurotubules. The main objectives of this investigation are to characterize the biochemical and pharmacological properties of microtubule proteins of the central nervous system. One line of investigation will center on the use of chemical agents which disrupt neurotubules (e.g., colchicine, vinblastine) in studies on the interactions of these agents with purified neurotubule subunits (tubulin) and in vitro reassembled neurotubules from chick embryo brain, and will involve the detailed characterization of neurotubule assembly in vitro. These studies will help increase our understanding of the mechanisms of neurotubule assembly, control of neurotubule assembly, and the mechanism of action of drugs which disrupt neurotubules. A second line of investigation will involve biochemical characterization of purified neurotubule protein subunits, and a comparison of the biochemical and pharmacological properties of neurotubule proteins from brains of different age with those from other sources. The purpose of these studies is to define the biochemical properties of microtubule proteins which are related to microtubule functions, with the long term goal of understanding the roles of neurotubules in relation to brain function. BIBLIOGRAPHIC REFERENCES: Margolis, R.L., and L. Wilson. Colchicine-Tubulin Complex Addition to Microtubule Ends: The Mechanism of Nonstoichiometric Colchicine "Poisoning". Abstract. Fed. Proc. 36:899 (1977). Asnes, C.F., and L. Wilson. Isolation of Bovine Brain Microtubule Protein: Maximum Yields Obtained by Utilizing Optimal Conditions for Polymerization. Abstract. VIIIth Int. Congress: Int. Soc. of Developmental Biologists. Aug. 1977 (Tokyo), in press.